Recruiting
Phase 1
Phase 2

Mirdametinib & Vinblastine

Sponsor:

St. Justine's Hospital

Code:

NCT06666348

Conditions

Pediatric Low-grade Glioma

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

Interventions

Mirdametinib

Study Details

Brief summary:

This is a 3-part open-label study (feasibility phase, treatment phase and follow-up phase) of orally administered mirdametinib in combination with intravenous vinblastine chemotherapy in patients with PLGG with activation of MAPK pathway.

Feasibility Phase:

The maximum tolerated/recommended phase 2 dose (MTD/RP2D) of the mirdametinib plus vinblastine combination will be assessed using a modified Rolling-6 design.

Treatment Phase:

Patients will receive mirdametinib twice daily (continuously) at a fixed dose (2mg/m2 po BID up to 4 mg BID) for a total of 13 cycles (28 days cycle). Weekly intravenous vinblastine at MTD will be given for a total of 17 cycles. If adverse events occur, two dose reductions are allowed.

Follow-up Phase:

Following the end of treatment, patients will be scheduled for a follow-up visit every 6 months for 36 months to evaluate PFS, TTP and OS.

Conditions

Pediatric Low-grade Glioma

Study ID

NCT06666348

Start date

Jan 12, 2026

Status verified date

Aug, 2026

Completion date

Apr, 2033

Anticipated

Primary completion date

Apr, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Signed written informed consent prior to study participation.
  • Study activities compliance: must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study, including disease assessment by contrast enhanced MRI.
  • Aged ≥ 2 years to ≤ 25 years when starting mirdametinib.
  • BSA ≥ 0,40m2
  • Diagnosis:

Participants must have PLGG with NF1 gene mutation (based on clinical NIH criteria, germline NF1 mutation or molecular analysis of the tumor) or PLGG with KIAA1549-BRAF fusion (based on molecular analysis of the tumor) or PLGG with evidence of MAPK pathway alteration with the exception of patients with BRAF V600E mutation (based on molecular analysis of the tumor).

  • Tumor tissue is required (at minimum, paraffin-embedded tissue block and additionally fresh frozen tissue \[if available\]). Patients with NF1 and Low Grade Glioma (LGG) can still be enrolled without tissue if no surgery or biopsy was conducted.
  • Baseline MRI.
  • Life expectancy greater than 6 months.
  • Lansky/Karnofsky score ≥ 50.
  • Normal organ and marrow function (see study protocol for specifics).
  • Female and male patients of fertile age must agree to use highly effective contraceptive measures.
  • Must be able to ingest by mouth and retain entirely the administered medication. Mirdametinib can not be administered via nasogastric tube or gastrostomy tube.

Exclusion Criteria:

  • Patients who are receiving other investigational agents.
  • Cardiac: QTcB ≥ 480 msec or an absolute resting left ventricular ejection fraction (LVEF) of ≤ 49%.
  • Patients who have any other malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
  • Tumor with BRAF V600E mutation.
  • Patients who received previous systemic or radiotherapy treatment.
  • Other severe and uncontrollable medical disease
  • Blood pressure higher than 95th percentile for patient's age, height and gender.
  • Increased risk of serious retinopathy and retinal vein occlusion.
  • Known diagnosis of human immunodeficiency virus infection, hepatitis B or C.
  • Previous major surgery within 2 weeks.
  • History of allergic reactions to compounds of similar chemical or biological composition to mirdametinib.
  • Pregnant or breastfeeding.

Study Design

Enrollment

50 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Mirdametinib + IV Vinblastine

Patients will receive oral mirdametinib twice daily (continuous) at a fixed dose (2mg/m2 PO BID, rounded to the nearest 1mg, up to a maximum of 4 mg BID) for a total of 13 cycles. Each cycle will last 28 days.

Interventions

Mirdametinib

Participants will receive orally administered mirdametinib in combination with intravenous vinblastine chemotherapy

Primary outcome measure

  • Determine maximum tolerated dose of Mirdametinib plus Vinblastine. [ Time Frame: 3 years ]
  • Determine the objective response rate of mirdametinib plus vinblastine for PLGG with Mitogen-activated Protein Kinase (MAPK) pathway activation in treatment naïve patients. [ Time Frame: 5 years ]

Central Contacts and Locations

Central contacts

Sébastien Perreault, M.D, FRCPC

514-345-4931s.perreault@umontreal.ca

MIRV Study Team

mirv.study.hsj@ssss.gouv.qc.ca

Locations

Alberta Children's Hospital

Recruiting

Calgary, Alberta, Canada, T3B 6A8

Contacts

Lucie Lafay-Cousin, MD

(403) 955-7272lucie.lafay-cousin@ahs.ca

Stollery Children's Hospital

Recruiting

Edmonton, Alberta, Canada, T6G 2E1

Contacts

Liana Nobre, MD

(780) 248-1646liana.nobre@albertahealthservices.ca

Childrens and Womens Health Centre of British Columbia - British Columbia Childrens Hospital

Recruiting

Vancouver, British Columbia, Canada, V6H 3V4

Contacts

Sylvia Cheng, MD

(604) 875-2406sylvia.cheng@cw.bc.ca

Cancer Care Manitoba

Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Contacts

Issai Vanan, MD

204-787-4156ctu_web@cancercare.mb.ca

Children's Hospital, London Health Sciences Centre

Recruiting

London, Ontario, Canada, N6A5W9

Contacts

Chantel Cacciotti, MD

(519) 685-8500chantel.cacciotti@lhsc.on.ca

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1E8

Contacts

Anthony Liu, MD

(416) 813-7654anthony.liu@sickkids.ca

Ashley Doka, CRPC

(416) 813-7654ashley.doka@sickkids.ca

CHU Sainte-Justine

Recruiting

Montreal, Quebec, Canada, H3T 1C5

Contacts

Sébastien Perreault, MD

514-345-4931s.perreault@umontreal.ca

Marie Galopin, RN

514-345-4931marie.galopin.hsj@ssss.gouv.qc.ca

CHU de Québec - Université Laval

Recruiting

Québec, Quebec, Canada, G1V 4G2

Contacts

Valérie Larouche, MD

(418) 525-4444valerie.larouche.med@ssss.gouv.qc.ca

CHU de Sherbrooke

Recruiting

Sherbrooke, Quebec, Canada, J1H 5N4

Contacts

Stéphanie Vairy, MD

819-346-1110stephanie.vairy@usherbrooke.ca

More Information

Sponsor

St. Justine's Hospital

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Keywords

  • PLGG
  • Pediatric PLGG
  • Pediatric
  • MAPK
  • NF1
  • KIAA1549-BRAF
  • pediatric low-grade glioma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by St. Justine's Hospital on 2026-08-11.